It is known that radio-iodine-labelled fatty acids are suitable for scintigraphic visualization of various organs such as the heart. Radioactive halogen-labelled fatty acids which accumulate most readily in the heart are those labelled with radio-iodine at the end of the chain, that is, at the omega-position. (Journal of Nuclear Medicine, 19:298 (1978).
Upon degradation via beta-oxidation, the remaining radioactive radical of omega-iodine fatty acids is present in the form of iodine which readily distributes throughout the blood and extracellular fluids. Consequently, scintigrams obtained utilizing these compounds do not represent the selective distribution of the radioactive fatty acid injected but rather the total radioactivity detected represents the sum distribution of both the radioactive fatty acid and the radioactive catabolite, iodide, throughout the entire blood and extracellular fluids. As a result, scintigrams of poor contrast are obtained such that fatty acid metabolism cannot be assessed quantitatively and marginal zones of infarct and ischemia regions cannot be clearly detected.
Chemical modification of fatty acids by terminal linkage of a phenyl radical has proved to have no influence on the biological activity of the novel agents of this invention, as compared to the activity of endogenous fatty acids. This is due to the fact that for these modified fatty acids, the hydrophobic character imparted by the long hydrocarbon chain and the hydrophilic center induced by the carboxylate group remain intact.
To be useful for scintigraphic applications for various organs of the body, it is necessary that radio-iodine-labelled omega phenyl fatty acids should readily accumulate in the organ to be imaged for diagnostic purposes. Biological transport mechanisms are of decisive importance. Transport of fatty acids throughout the blood, for example to the myocardial tissue, is effected by a transport protein, albumin, to which fatty acids are bound by both electrostatic and hydrophobic forces. Transport of fatty acids into cells utilizing them first requires the release of the fatty acid from the albumin protein complex. Therefore, the bond between the modified fatty acid and the albumin complex cannot be stronger than that of the bond between endogenous fatty acids and albumin. For transport across the cell membrane, the degree of liposolubility predetermined by the hydrophobic chain end is of decisive importance. Studies using alkane fatty acids have revealed that replacement of the hydrophobic methyl group by an iodine atom does not alter the biochemical and physiological properties of the fatty acid. There is also the difference with respect to these properties between an iodine-labelled phenyl fatty acid and endogenous fatty acids.
Diagnostic utilization of omega-iodine fatty acids is made feasible only through the use of a special correction process whereby the iodine-induced radioactive background can be subtracted from the total radioactivity detected. Accordingly, 30 minutes after administration of the labelled fatty acid, a known amount of radioactive iodide is injected as an internal standard. Knowing how much radioactive iodide was injected as an internal standard, it is then possible to calculate what proportion of the total radioactivity detected is due to the iodide-induced background and to correct the scintigram accordingly. In this way, scintigrams of good quality are obtained, such that localized rates of fatty acid catabolism in heart and liver tissue can be determined.